Neoplasia Dr. Gehan Mohamed

Learning objectives Understand the definition of neoplasia. List the Classification of neoplasia. Describe the General characters of benign tumors. Understand the Nomenclature of benign tumors. Nomenclature of Malignant tumors. Nomenclature of some Malignant tumors with Exceptions. Describe etiology of malignant tumors

Learning objectives definition,Microscopic changes and types of dysplasia. Describe Pathogenesis of tumor formation. Describe General characters of malignant tumors. Understand method of gading and stagging of Malignant Neoplasms. Understand definition of Carcinoma in-situ Describe methods of Spread of malignant tumors. Describe laboratory diagnosis of malignant tumors. Identify the causes of death in malignant tumors. Describe the paraneoplastic syndrome.

Neoplasia Neoplasia = new growth Neoplasm = onco tumor = swelling The study of neoplasms = Oncology Onco = tumor + ology=study

Neoplasia Definition: It is a self controlling growth formed by unlimited multiplication of abnormal cells

Neoplasia Classification Benign Malignant Locally malignant tumors Epithelial Mesenchymal Malignant Primary Epithelial (carcinoma) Mesenchymal (sarcoma) Secondary (metastatic) Locally malignant tumors

General characters of benign tumors Pathology Gross pathology Size: Usually small in size Shape: usually ovoid or rounded in shape Capsule: usually capsulated Cut section solid or cystic Hemorrhage and necrosis: usually absent Microscopic pathology Differentiation: The cells are well differentiated i.e tumor cells closely similar to the tissue of origin. Nucleocytoplasmic ratio (N/C) ratio: small or normal Stroma: is usually well formed with few blood vessels

Behavior of benign tumors Rate of growth: usually slow Mode of growth: by expansion Localization: usually localized Effects on the host: usually do not destroy the surrounding structures and do not kill the patient (except in certain sites as in brain) Recurrence: usually not recurrent Metastasis: Do not metastatise Malignant change: may occur

Benign tumors Nomenclature Benign tumors: prefix + suffix Type of cell + (-oma)

Neoplasia Examples: Benign tumor arising in fibrous tissue: Fibro + oma = Fibroma Benign tumor arising in fatty tissue: Lipo + oma = lipoma

Benign epithelial tumors Benign mesenchymal tumors Papilloma Adenoma Benign mesenchymal tumors CT tumors Fibroma Lipoma Chondroma Osteoma Benign tumors of muscles Leiomyoma Rhabdomyoma Benign tumors of vessels Haemangioma lymphangioma

Lipoma

Chondroma

Adenoma : benign epithelial neoplasms producing gland pattern… Adenoma : benign epithelial neoplasms producing gland pattern….OR … derived from glands but not necessarily exhibiting gland pattern Examples : Respiratory airways: Bronchial adenoma Renal epithelium: Renal tubular adenoma Liver cell : Liver cell adenoma Papilloma : benign epithelial neoplasms growing on any surface that produce microscopic or macroscopic finger-like pattern Squamous epithelium: squamous papilloma

Adenoma

Fibroadenoma

Papilloma

Malignant tumors have two basic components: Parenchyma: made up of neoplastic cells Stroma: made up of non-neoplastic, host-derived connective tissue and blood vessels. The parenchyma: Determines the biological behavior of the tumor From which the tumor derives its name The stroma: Carries the blood supply Provides support for the growth of the parenchyma

Adenocarcinoma formed of malignant glands and stroma

Malignant tumors: Malignant tumor arising in mesenchymal tissue : SARCOMA From fibrous tissue: Fibrosarcoma From bone : Osteosarcoma From cartilage : chondrosarcoma

Osteosarcoma

Malignant tumors arising from epithelial origin : CARCINOMA Squamous cell carcinoma Renal cell adenocarcinoma cholangiocarcinoma

Carcinomas arising from any epithelium of the body that exhibit squamous differentiation are termed squamous cell carcinoma.

Papillary Cystadenocarcinoma of the Ovary Nomenclature other descriptive terms may be added such as: Papillary Cystadenocarcinoma of the Ovary

Nomenclature of some Malignant tumors with Exceptions Melanoma ( skin ) Mesothelioma (mesothelium ) Seminoma ( testis ) Lymphoma ( lymphoid tissue )

Neoplasm (Tumors) Etiology of malignant tumors A- Precancerous lesions Examples of some lensions that exhibit a tendency to undergo malignant transformation 1- Endometrial hyperplasia endometrial carcinoma. 2- Fibrocystic disease of the breast cancer breast 3- Liver cirrhosis hepatocellular carcinoma

Dysplasia Definition:Abnormal development or growth of cells (i.e maturation abnormality). Commonest sites : Cervix(cervical intraepithelial neoplasia) (CIN) Vagina(vaginal intraepithelial neoplasia) ( VIN). bronchi(bronchial intraepithelial neoplasia BIN)

Microscopic changes of dysplasia Dysplasia is characterized by : -Anisocytosis (cells of unequal size) -Poikilocytosis (cells of variable shape) -Hyperchromatism -Presence of mitotic figures (an unusual number of cells which are currently dividing).

Types of dysplasia 1- low grade dysplasia: -not affect the whole thickness of epithelium. -it is reversible if the irritant is removed. High grade dysplasia: - it is precancerous (not reversible) -affect the whole thickness of epithelium. -it is also called carcinoma in situ as the basement membrane not invaded by the abnormal cells

Here, there is normal cervical squamous epithelium at the left, but dysplastic squamous epithelium at the right. The dysplastic epithelial cells are darker, smaller, and more crowded,. Dysplasia is still confined to the epithelium. Dysplasia is still reversible.

At high magnification, the normal cervical squamous epithelium at the left merges into the dysplastic squamous epithelium at the right in which the cells are more disorderly and have darker nuclei with more irregular outlines.

This is "carcinoma in situ" because the carcinoma is still confined to the epithelium, as the entire portion of epithelium is composed of abnormal cells and the basement membrane is still intact.

This is invasive squamous cell carcinoma This is invasive squamous cell carcinoma.the squamous epithelial cells in these large nests with pink keratin in the centers.

Neoplasm (Tumors) Etiology of tumors A- Precancerous lesions 4- Squamous metaplasia lead to squamous cell carcinoma as in : a- Urinarry bladder in bilharziasis b- Bronchial mucosa with chronic bronchitis and smoking 5- Benign tumors a- Papilloma of urinary bladder b- Adenoma of thyroid or colon

Neoplasm (Tumors) Etiology of tumors B- Helping factors (Cocarcinogens) 1- Age With aging there is a more chance of exposure to the carcinogen 2- Sex Most of tumors are common in male

Neoplasm (Tumors) Etiology of tumors B- Helping factors (Cocarcinogens) 3- Diet Fat may be related to colonic cancer. Smoked fish is related to gastric carcinoma. Excess alcohol is related to liver cancer. 4- Smoking May lead to lung cancer 5- Heredity Some tumors are inherited i.e. retinoblastoma and colonic cancer

Neoplasm (Tumors) Etiology of tumors C- Carcinogens Types of carcinogens 1- Chemical carcinogens Methylated hydrocarbons-A 20 dyes bladder cancer Aflatoxins produced from Aspergillus fungus liver cancer 2- Viruses Hepatitis B virus liver cancer Human papilloma virus cancer cervix

Neoplasm (Tumors) Etiology of malignant tumors C- Carcinogens 3- Radiations Ionizing radiation, ultraviolet or prolonged exposure to sunlight Cancer of the skin Leukemia

Neoplasm (Tumors) Etiology of malignant tumors C-mechanism of action of Carcinogens Chemical carcinogens, viruses and radiation result in DNA damage and initiation of cancer by : 1- Activation of oncogenes e.g myc gene,K-ras (genes responsible for abnormal growth and proliferation of cell). 2- Inactivation of cancer suppressor genes e.g RB ,P53 genes.

Neoplasm (Tumors) Etiology of tumors C-mechanism of action of Carcinogens Hormones act as promoters i.e. they stimulate the proliferation of the already transformed cells e.g. Estrogen cancer breast and endometrial cancer Androgen prostatic cancer

Pathogenesis of tumor formation

General characters of malignant tumors Pathology Gross pathology Size: Usually reach large size Shape Polypoid or fungating mass in tumors of solid organs Malignant ulcer in tumors of surface epithelium Infiltrating annular mass in tumors of hollow organs Capsule: non-capsulated Cut section sold or cystic Hemorrhage and necrosis: common Microscopic pathology Differentiation: The cells show loss of differentiation The cells show some or all features of malignancy as loss of polarity of the cells ,hyperchromatic neuclei, increase N/C ratio,abnorml mitosis and prominent neucleolus. Stroma: is usually desmoplastic with rich vascularity

Behavior of malignant tumors Rate of growth: usually rapid Mode of growth: by infiltration Localization: usually not localized Effects on the host: can kill the patient wherever present Recurrence: may recur Metastasis: may occur Precancerous lesions Chronic inflammatory lesions Hyperplastic lesions Some benign tumors Other lesions as peptic ulcer and un-descended testis

Grading of Malignant Neoplasms Grade Definition I Well differentiated II Moderately differentiated III Poorly differentiated IV Nearly anaplastic

Oat cell carcinima of the lung Undifferenciated carcinoma Grade IV Poorly differentiated neoplasms have cells that are difficult to recognize as to their cell of origin. Higher grade means: a lesser degree of differentiation and the worse the biologic behavior Adenocarcinoma of the colon Well differenciated carcinoma A well differentiated neoplasm is composed of cells that closely resemble the cell of origin.

Clinical Staging T (primary tumor): T1, T2, T3, T4 N (regional lymph nodes): N0, N1, N2, N3 M (metastasis): M0, M1

TNM staging system in cancer

Staging of Malignant Neoplasms Stage Definition Tis In situ, non-invasive (confined to epithelium) T1 Small, minimally invasive within primary organ site T2 Larger, more invasive within the primary organ site T3 Larger and/or invasive beyond margins of primary organ site T4 Very large and/or very invasive, spread to adjacent organs N0 No lymph node involvement N1 Regional lymph node involvement N2 Extensive regional lymph node involvement N3 More distant lymph node involvement M0 No distant metastases M1 Distant metastases present

Carcinoma in-situ Definition: an intraepithelial malignancy in which malignant cells involve the entire thickness of the epithelium without penetration of the basement membrane. Applicable only to epithelial neoplasm

Carcinoma in situ

Spread of malignant tumors Mechanism of spread Invasion of the matrix Vascular dissemination and homing of tumor cells Routes of spread Direct or local spread Malignant cells infiltrates the surrounding structures in all direction Distant spread: as Lymphatic spread Lymphatic permeation Lymphatic embolization Blood spread Course of tumor emboli Organ metastasis Transcoelomic spread Spread by implantation

Localy malignant tumors Definition Groups of malignant tumors that spread only locally Characters Slow rate of growth Spread only locally by direct infiltration The cells show features of malignancy Examples Basal cell carcinoma of skin Osteoclastoma Adamantinoma in jaw Bronchial adenoma Carcinoid tumor Astrocytoma in brain Craniopharyngioma from pituitary gland

Laboratory Diagnosis of malignant tumors Morphologic methodes Biochemical assays Molecular diagnosis

Laboratory Diagnosis Microscopic Tissue Diagnosis the gold standard of cancer diagnosis. Several sampling approaches are available: Excision or biopsy Frozen section fine-needle aspiration Cytologic smears

Immunohistochemical diagnosis

Laboratory Diagnosis Biochemical assays: Useful for measuring the levels of tumor associated enzymes, hormones, and tumor markers in serum. Useful in determining the effectiveness of therapy and detection of recurrences after excision Only few tumor markers are proved to be clinically useful, example CEA in colonic adenocarcinoma and α- fetoprotein in hepatoma.

Molecular diagnosis Polymerase chain reaction (PCR) example: detection of BCR-ABL transcripts in chronic myeloid leukemia. Fluorescent in situ hybridization (fish) it is useful for detecting chromosomes translocation characteristic of many tumors Both PCR and Fish can show amplification of oncogenes (HER2 and N-MYC)

Neoplasm (Tumors) Causes of death in malignant tumors 1- Destruction of vital tissues such as brain, liver, kidney 2- Malnutrition due to interference of food intake, digestion and absorption. 3- Obstructive effects e.g. urinary tract obstruction. 4- Anemia due to a- Continuous blood loss from bleeding malignant ulcers. b- Destruction of red bone marrow by metastatic deposites. 5- Malignant cachexia with wasting, loss of weight and muscular weakness. 6- Secondary infection by bacteria, viruses and fungi.

Paraneoplastic syndromes They are symptoms that occur in cancer patients due to secretion of some hormone like substances and not due to distant metastasis. They are diverse and are associated with many different tumors. They appear in 10% to 15% of pateints. They may represent the earliest manifestation of an occult neoplasm. They may represent significant clinical problems and may be lethal. They may mimic metastatic disease.

The most common paraneoplastic syndrome are: Hypercalcemia Cushing syndrome Nonbacterial thrombotic endocarditis The most often neoplasms associated with these syndromes: Lung and breast cancers and hematologic malignancies